Dietary vitamin A consumed by pregnant mice is converted into retinoic acid, which is essential to fetal immune system development.

Dietary vitamin A consumed by pregnant mice is converted into retinoic acid, which is essential to fetal immune system development.

Vitamin A has long been known to help adult immune systems fight bacterial and fungal pathogens. But a study in mice suggests that the vitamin may also be essential for setting up the immune system much earlier—while a fetus is in utero.

According to a new study in ﻿Nature, pregnant mice whose diet lacked vitamin A produced offspring with smaller-than-normal lymph nodes (2014, DOI: 10.1038/nature13158). Lymph nodes are essential for development and long-term maintenance of the immune system. The team of researchers—led by Henrique Veiga-Fernandes of the Institute of Molecular Medicine, in Lisbon—also found that offspring born from female mice deprived of vitamin A during pregnancy have weaker-than-normal immune responses as adults.

“A mother’s diet has irreversible consequences for the embryo’s immune system,” Veiga-Fernandes says. “This period of time is absolutely critical: Vitamin A preprograms the immune system for later in life.” He suggests the strong similarities between the development of the immune system in mice and humans mean that these conclusions likely hold for both species.

When a pregnant woman consumes vitamin A, enzymes quickly convert it to retinoic acid. Veiga-Fernandes’s team discovered that in the growing mouse fetus, retinoic acid activates gene expression to trigger the production of a hormone receptor called RORγt. This receptor orchestrates the production and maturation of type 3 innate lymphoid cells. These cells not only establish lymph node tissues in the fetus but also help launch immune responses to pathogens later in life.

In the U.S. and Europe, most pregnant women satisfy their fetuses’ needs for vitamin A with a normal diet. In fact, too much vitamin A can lead to headaches, vomiting, loss of maternal bone density and birth defects, Veiga-Fernandes says. However, in developing nations, diets are often lacking in vitamin A.

“This work has major implications,” comments Hilde Cheroutre, at La Jolla Institute for Allergy & Immunology. It stresses the significant impact of nutrition quality and quantity during pregnancy, she adds, “not only for the general development of the embryo but also for the overall health and disease resistance of the individual throughout its lifetime.”